By: Kyra Newmaster, MD/PhD Candidate
Have you ever misplaced your keys and then laughed it off as getting old? Some memory loss is common in old age, but unfortunately severe memory loss is a sign of Alzheimer’s Disease (AD). This neurodegenerative disease is thought to be caused by the build-up of the sticky molecule like amyloid β in the brain.
Patients with this disease often have changes in personality and become unable to care for themselves leading to medical costs of $604 billion dollars worldwide in 2010. Despite the rapidly growing economic burden of this disease and increased research into the disease there is still a large debate about what truly causes AD. If we can find the cause, we might stand a fighting chance at stopping its insidious roll.
One theory suggests changes in brain metabolism could contribute to development of AD. These changes may involve increased resistance to insulin (the underlying mechanism of type II Diabetes) and an altered fat utilization.
Research investigated metabolic changes in the brain of AD mice
Based on this theory, Dr. Zheng and his colleague asked what other metabolic changes occur in the brain, and is there a pattern over time?
Scientists cannot evaluate the answers to this question easily in humans. Obviously, cutting the brian open and looking has some ethical and logistical difficulties. Therefore, the authors used mice that have a genetic mutation similar to one that is highly linked to human AD (mutations in APP/PS1). When the mutant and normal mice reached either 1 month, 5 months, or 10 months of age, they were tested for memory using a test known as the Morris Water Maze. The test requires mice to learn and remember where a hidden platform is in a tank of water. If the mouse takes longer or searches in the wrong areas, scientists interpret this as reduction in memory function.
After testing for memory, the scientists used Nuclear Magnetic Resonance (NMR) (a way to measure amounts of molecules) to identify metabolic by-products in different brain regions.
When comparing Alzheimer’s mice to normal mice, only mice the oldest mice showed reduced memory. However, NMR analysis showed increase in metabolites before the onset of memory problems. This suggests that metabolic brain changes are occurring before memory symptoms.
One region that stood out: the hypothalamus
The hypothalamus is a small region on the bottom of the brain that is responsible for releasing hormones that control our stress response, metabolism, and sleep-wake cycles.
It is also special, because it monitors blood chemicals. Most of the brain is protected from blood by the blood-brain barriers. This ensures that when you get a cold, you don’t get a brain infection. However, the hypothalamus needs to monitor blood to let your brain know what is circulating to the rest of the body.
The hypothalamus may be a region affected in early AD
Altered metabolism in this region may change how the brain regulates bodily functions like blood sugar and vice versa. Changes in the blood like high blood sugar may impact the metabolic function of the hypothalamus leading to AD or worsening the symptoms. Indeed, AD associated molecules have been found in the hypothalamus of diabetic mice.
Finally, this means that the hypothalamus may be part of inducing AD, and because the changes in the hypothalamus precede apparent mental decline, the hypothalamus may be a good target for developing earlier diagnostic strategies.